A Comparison of Acutely Isolated Human Ventricular Myocytes with Stem Cell Derived Cardiocytes

Abstract

Recent studies have characterized cardiac ionic currents in cardiocytes derived from human induced pluripotent stem cells. However, direct comparison with human ventricular myocytes is hampered by differences in experimental conditions. Similarly, stem cell derived cardiocytes are different and potentially more variable than native myocytes. We examined commercially prepared cells (iCells) and scale production cells (hIPS-CMs) using electronic expression of IK1 to distinguish ventricular cells, compared with myocytes (VM) from biopsy samples.APs were recorded in VM, iCells and hiPSC-CMs. iCells and hiPSC-CMs had depolarized membrane potentials, slower upstroke velocities, and prolonged AP relative to VM. These differences were minimized by electronic expression of IK1. Capacitances were larger in VM (298.97 ± 27.5 pF (4 hearts, n=44)) than in iCells (73.21 ± 5.4 (n=32), p<0.05) and hIPS-CMs (64.25 ± 4.94 (n=75), p<0.05). At −120 mV, a large IK1 was observed in VM (−14.3 ± 1.36 pA/pF (4 hearts, n=44)); IK1 was much smaller in iCells (−1.73 ± 0.92 (n=19), p<0.01) and hIPS-CMs (−2.54 ± 0.49 (n=29), p<0.01). VM had larger peak outward (Ito) currents at +50 mV (6.2 ±- 0.7 pA/pF (n=44, four hearts)) than iCells (2.6 ± 0.2 (n=19, p<0.01)) and hIPS-CMs (2.9 ± 0.3 (n=29, p<0.01)) but all had similar variability relative to current density. Large sodium currents were recorded at 0 mV in VM (−23.7 +/− 3.4 pA/pF (4 hearts, 32 myocytes)) as well as in iCells (−26.1 +/− 3.2 (n=14)) and in hiPSC-CMs (−17.0 +/− 4.1 (n=16)) with high degrees of variability for all cell types. In conclusion, there are functional differences between VM and stem cell derived cell types, but minimal differences between stem cell derived cardiocytes based on source. Similarly, cell to cell variability was similar regardless of source.